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https://www.readbyqxmd.com/read/29021222/the-perivascular-pathways-for-influx-of-cerebrospinal-fluid-are-most-efficient-in-the-midbrain
#1
Howard Dobson, Matthew MacGregor Sharp, Richard Cumpsty, Theodore P Criswell, Tyler Wellman, Ciara Finucane, Jenna M Sullivan, Roy O Weller, Ajay Verma, Roxana O Carare
Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial basement membranes of arteries. This project tested the hypotheses that pial-glial basement membranes of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF...
October 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28993710/dose-dependent-expression-of-claudin-5-is-a-modifying-factor-in-schizophrenia
#2
C Greene, J Kealy, M M Humphries, Y Gong, J Hou, N Hudson, L M Cassidy, R Martiniano, V Shashi, S R Hooper, G A Grant, P F Kenna, K Norris, C K Callaghan, M dN Islam, S M O'Mara, Z Najda, S G Campbell, J S Pachter, J Thomas, N M Williams, P Humphries, K C Murphy, M Campbell
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells...
October 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28977413/identification-of-the-synthetic-cannabinoid-1-4-cyanobutyl-n-2-phenylpropan-2-yl-1h-indazole-3-carboxamide-cumyl-4cn-binaca-in-plant-material-and-quantification-in-post-mortem-blood-samples
#3
Oya Yeter
In May 2016, a new type of synthetic indazole-3-carboxamide cannabinoid (CUMYL-4CN-BINACA) was detected in seized plant material submitted to the Istanbul Council of Forensic Medicine by the National Police Office. The major ingredient in this material was purified using preparative liquid chromatography, and its structure was identified using liquid chromatography-high-resolution mass spectrometry (LC-HR/MS), gas chromatography-electron ionization/mass spectrometry (GC-EI/MS), nuclear magnetic resonance (NMR) spectroscopy and Fourier transform-infrared spectroscopy (FT-IR)...
August 31, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28973645/alpha-synuclein-induces-the-unfolded-protein-response-in-parkinson-s-disease-snca-triplication-ipsc-derived-neurons
#4
Sabrina M Heman-Ackah, Raquel Manzano, Jeroen J M Hoozemans, Wiep Scheper, Rowan Flynn, Wilfried Haerty, Sally A Cowley, Andrew R Bassett, Matthew J A Wood
The recent generation of induced pluripotent stem cells (iPSCs) from a patient with Parkinson's disease (PD) resulting from triplication of the α-synuclein (SNCA) gene locus allows unprecedented opportunities to explore its contribution to the molecular pathogenesis of PD. We used the double-nicking CRISPR/Cas9 system to conduct site-specific mutagenesis of SNCA in these cells, generating an isogenic iPSC line with normalized SNCA gene dosage. Comparative gene expression analysis of neuronal derivatives from these iPSCs revealed an ER stress phenotype, marked by induction of the IRE1α/XBP1 axis of the unfolded protein response (UPR) and culminating in terminal UPR activation...
September 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28942032/post-mortem-review-of-fentanyl-related-overdose-deaths-among-identified-drug-users-in-southern-bavaria-germany-2005-2014
#5
Inga Sinicina, Hans Sachs, Wolfgang Keil
BACKGROUND: Two decades ago, there were only single case reports on deaths in Europe following the consumption of illicitly manufactured fentanyl by problem drug users. Today, lethal fentanyl intoxication is now no longer a rarity. Since 2005, a rapid increase of lethal fentanyl-related intoxications in the drug scene has been observed at the Institute of Legal Medicine, Ludwig Maximilians University, Munich. We hypothesized that this rise is the result of the launch of fentanyl matrix patches in Germany in 2004, their broad acceptance, their diversion from the regulated supply chain, and incautious prescription by medical care providers...
September 14, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28941755/the-diagnostic-value-of-fdg-and-amyloid-pet-in-alzheimer-s-disease-a-systematic-review
#6
REVIEW
Louise Rice, Sotirios Bisdas
PURPOSE: By 2050 it is projected that 115 million people worldwide will have Alzheimer's Disease (AD) [1]. Recent attempts have been made to redefine the diagnostic criteria of AD to include markers of neurodegeneration - measurable by FDG-PET - and markers of amyloid accumulation - measurable by amyloid-PET. MATERIALS AND METHODS: A systematic review of the literature was performed to examine the current diagnostic use of amyloid and FDG PET. MEDLINE and EMBASE databases and the Cochrane Database were searched for relevant papers RESULTS AND DISCUSSION: This search resulted in twenty-nine papers on amyloid imaging, twenty-three papers on FDG-PET and eight papers which utilized both techniques...
September 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28924203/the-common-variants-implicated-in-microstructural-abnormality-of-first-episode-and-drug-na%C3%A3-ve-patients-with-schizophrenia
#7
H Y Ren, Q Wang, W Lei, C C Zhang, Y F Li, X J Li, M L Li, W Deng, C H Huang, F Du, L S Zhao, Y C Wang, X H Ma, X Hu, T Li
Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894300/striatal-dopamine-d1-type-receptor-availability-no-difference-from-control-but-association-with-cortical-thickness-in-methamphetamine-users
#8
K Okita, A M Morales, A C Dean, M C Johnson, V Lu, J Farahi, M A Mandelkern, E D London
Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28893562/positive-allosteric-modulation-of-m1-and-m4-muscarinic-receptors-as-potential-therapeutic-treatments-for-schizophrenia
#9
REVIEW
Samantha E Yohn, P Jeffrey Conn
Current antipsychotic drugs provide symptomatic relief for positive symptoms of schizophrenia, but do not offer symptom management for negative and cognitive symptoms. In addition, many patients discontinue treatment due to adverse side effects. Therefore, there is a critical need to develop more effective and safe treatment options. Although the etiology of schizophrenia is unclear, considerable data from post-mortem, neuroimaging and neuropharmacology studies support a role of the muscarinic acetylcholine (mAChRs) in the pathophysiology of schizophrenia...
September 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28841781/non-medical-use-of-psychoactive-prescription-drugs-is-associated-with-fatal-poisoning
#10
Jari Haukka, Pirkko Kriikku, Claudia Mariottini, Timo Partonen, Ilkka Ojanperä
AIMS: The aims of this study were to estimate the prevalence and predictors of non-medical substance use, and to assess the association between non-medical substance use and fatal poisoning or history of drug abuse in Finland. DESIGN AND SETTING: Retrospective cohort study of all medico-legally investigated death cases in Finland. The post-mortem toxicology database was linked together with the register on reimbursed prescription medicines. PARTICIPANTS/CASES: All post-mortem cases between 2011 and 2013 positive for one or more of the following drugs: oxycodone, fentanyl, tramadol, clonazepam, gabapentin, pregabalin, tizanidine, olanzapine, quetiapine, risperidone, alprazolam, zolpidem, mirtazapine, and bupropion, n=2974...
August 25, 2017: Addiction
https://www.readbyqxmd.com/read/28820985/human-bone-marrow-as-a-tissue-in-post-mortem-identification-and-determination-of-psychoactive-substances-screening-methodology
#11
Renata Wietecha-Posłuszny, Sofia Lendor, Magdalena Garnysz, Marcin Zawadzki, Paweł Kościelniak
The aim of this study was to apply a new instrumental approach to the analysis of human bone marrow for forensic purposes. A new screening method for the detection of more than 30 psychoactive drugs in bone marrow was developed and applied to case samples. The drugs used in this study belonged to the following groups: benzodiazepines (BZDs, n=16), tricyclic antidepressants (TCAs, n=5), selective serotonin reuptake inhibitors (SSRI, n=4), serotonin-norepinephrine reuptake inhibitors (n=1), anticonvulsants (n=1), imidazopyridines (n=1) and piperazines (n=3)...
September 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28820437/are-astrocytes-the-predominant-cell-type-for-activation-of-nrf2-in-aging-and-neurodegeneration
#12
REVIEW
Jeffrey R Liddell
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates hundreds of antioxidant genes, and is activated in response to oxidative stress. Given that many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and multiple sclerosis are characterised by oxidative stress, Nrf2 is commonly activated in these diseases. Evidence demonstrates that Nrf2 activity is repressed in neurons in vitro, and only cultured astrocytes respond strongly to Nrf2 inducers, leading to the interpretation that Nrf2 signalling is largely restricted to astrocytes...
August 18, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28781208/the-blood-brain-barrier-in-psychosis
#13
REVIEW
Thomas A Pollak, Svetlana Drndarski, James M Stone, Anthony S David, Philip McGuire, N Joan Abbott
Blood-brain barrier pathology is recognised as a central factor in the development of many neurological disorders, but much less is known about the role of the blood-brain barrier in psychiatric disorders. We review post-mortem, serum-biomarker, CSF-biomarker, and neuroimaging studies that have examined blood-brain barrier structure and function in schizophrenia and related psychoses. We consider how blood-brain barrier dysfunction could relate to glutamatergic and inflammatory abnormalities, which are increasingly understood to play a part in the pathogenesis of psychosis...
August 3, 2017: Lancet Psychiatry
https://www.readbyqxmd.com/read/28733105/adverse-reactions-of-%C3%AE-2-adrenoceptor-agonists-in-cats-reported-in-2003-2013-in-finland
#14
Marja R Raekallio, Marika Virtanen, Irmeli Happonen, Outi M Vainio
OBJECTIVE: To describe suspected adverse drug reactions in cats associated with use of α2-adrenoceptor agonists. STUDY DESIGN: Retrospective study. ANIMALS: A total of 90 cats. METHODS: Data were collected from reports on adverse reactions to veterinary medicines sent to the Finnish Medicines Agency during 2003-2013. All reports of suspected adverse reactions associated with use of α2-adrenoceptor agonists in cats were included...
March 1, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28710498/gene-network-dysregulation-in-dorsolateral-prefrontal-cortex-neurons-of-humans-with-cocaine-use-disorder
#15
Efrain A Ribeiro, Joseph R Scarpa, Susanna P Garamszegi, Andrew Kasarskis, Deborah C Mash, Eric J Nestler
Metabolic and functional alterations of neurons in the dorsolateral prefrontal cortex (dlPFC) are thought to contribute to impulsivity, which is a hallmark of addictive behaviors that underlie compulsive drug seeking and taking in humans. To determine if there is a transcriptional signature in dlPFC neurons of humans with cocaine use disorder, we performed total RNA-sequencing on neuronal nuclei isolated from post-mortem dlPFC of cocaine addicts and healthy controls. Our results point toward a transcriptional mechanism whereby cocaine alters specific gene networks in dlPFC neurons...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28689687/the-effect-of-the-muscarinic-m1-receptor-antagonist-biperiden-on-cognition-in-medication-free-subjects-with-psychosis
#16
Claudia Vingerhoets, Geor Bakker, Jelske van Dijk, Oswald J N Bloemen, Ya Wang, Raymond C K Chan, Jan Booij, Therese A M J van Amelsvoort
The acetylcholine muscarinic M1 receptor has been implicated in both psychosis and cognition. Post-mortem research has shown reduced muscarinic M1 receptor density in 25% of chronic patients with schizophrenia. It is unknown whether reduced M1 receptor density is related to cognitive symptoms of psychosis. We investigated the role of the M1 receptor in separate cognitive domains in subjects with a psychotic disorder using a muscarinic M1 antagonist as an acute pharmacological challenge. 33 young subjects with a psychotic disorder and 30 gender, age and IQ matched healthy controls were enrolled...
July 6, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28686693/ivermectin-treatment-of-loa-loa-hyper-microfilaraemic-baboons-papio-anubis-assessment-of-microfilarial-load-reduction-haematological-and-biochemical-parameters-and-histopathological-changes-following-treatment
#17
Samuel Wanji, Ebanga-Echi J Eyong, Nicholas Tendongfor, Che J Ngwa, Elive N Esuka, Arnaud J Kengne-Ouafo, Fabrice R Datchoua-Poutcheu, Peter Enyong, Dalen Agnew, Rob R Eversole, Adrian Hopkins, Charles D Mackenzie
BACKGROUND: Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28681613/the-toxicological-significance-of-post-mortem-drug-concentrations-in-bile
#18
Robin E Ferner, Jeffrey K Aronson
CONTEXT: Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value. AIM: To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature...
July 6, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28656354/nonfatal-and-fatal-intoxications-with-pure-caffeine-report-of-three-different-cases
#19
Jan Magdalan, Marcin Zawadzki, Rafał Skowronek, Magdalena Czuba, Barbara Porębska, Tomasz Sozański, Paweł Szpot
Caffeine is not usually perceived as a drug by most people because it is found in many foods and drinks, including caffeinated energy drinks, as well as in over the counter analgesics and cold preparations. Recently in Poland it has become increasingly common to take pure caffeine, bought through online stores, as a psychoanaleptic. This creates a much higher risk of severe and even fatal poisoning in comparison with the risk associated with the abuse of food products and non-prescription medicines containing low doses of caffeine...
June 27, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28650104/alzheimer-s-disease-and-metabolic-syndrome-a-link-from-oxidative-stress-and-inflammation-to-neurodegeneration
#20
REVIEW
Eduardo Rojas-Gutierrez, Guadalupe Muñoz-Arenas, Samuel Treviño, Blanca Espinosa, Raúl Chavez, Karla Rojas, Gonzalo Flores, Alfonso Díaz, Jorge Guevara
Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles (NFT). Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome (MetS) and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage...
June 26, 2017: Synapse
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